AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) has received approval from the US Food and Drug Administration (FDA) for an expanded indication of breast cancer patients with very low levels of HER2 protein.
The drug is now cleared for use in adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who have progressed on at least one endocrine therapy in the metastatic setting.
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By GlobalDataEnhertu first secured approval in 2019 for patients with high levels of HER2, a protein that promotes cancer cell growth. In 2022, the drug became the first therapy approved for HER2-low breast cancer. Dave Fredrickson, executive vice president of the oncology haematology business at AstraZeneca, said that this new indication broadens the patient population who are eligible for treatment with Enhertu.
HER2-ultralow refers to tumours that have extremely low levels of the HER2 protein, but still exhibit some detectable membrane staining on immunohistochemistry (IHC). Traditionally, breast cancers were categorised as either HER2-positive, or HER2-negative. The introduction of the HER2-low category in 2022 expanded treatment options for some patients with reduced HER2 expression. The HER2-ultralow classification further refines this spectrum.
The approval also allows certain patients to receive Enhertu earlier in their treatment course. Previously, it was typically used after both endocrine therapy and chemotherapy. Under the new indication, eligible patients can receive Enhertu after endocrine therapy, without first undergoing chemotherapy.
The decision was supported by data from the Phase III DESTINY-Breast06 trial, which showed a 36% reduction in the risk of disease progression or death in patients treated with Enhertu compared to chemotherapy. Median progression-free survival was 13.2 months with Enhertu, compared to 8.1 months in the chemotherapy arm. The trial also indicated that HER2-ultralow patients responded similarly to those in the HER2-low group.
Enhertu has been a major commercial success for AstraZeneca and Daiichi Sankyo, generating $3bn in revenue in 2023, as per the company financials. According to GlobalData’s Pharma Intelligence Center, the drug is projected to reach $13.9bn in sales by 2030.
GlobalData is the parent company of Pharmaceutical Technology.
Despite Enhertu’s blockbuster status, market access remains a challenge in certain regions. In November 2024, the UK’s National Institute for Health and Care Excellence (NICE) rejected Enhertu for HER2-low breast cancer, marking the third failed attempt to secure a deal for its reimbursement.
Despite months of negotiations involving NHS England and direct intervention from UK Health Secretary Wes Streeting, a pricing agreement could not be reached. NICE stated that discussions ended without an agreement on cost-effectiveness, despite offering what it described as “as much flexibility as possible”.
The latest FDA approval comes shortly after AstraZeneca and Daiichi Sankyo secured another regulatory win in oncology. Earlier this month, the regulator approved the TROP2-directed ADC Datroway (datopotamab deruxtecan) for HR-positive, HER2-negative breast cancer in patients previously treated with endocrine-based therapy and chemotherapy. The drug was a product of the 2020 global development and commercialisation agreement between the two companies, which was worth $6bn.
ADC content on Pharmaceutical Technology (Or Clinical Trials Arena) is supported by Syngene. Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content.
